Comparison of intravenous terlipressin infusion versus bolus in patients with acute-on-chronic liver failure–acute kidney injury – an open label RCT

Aim of the study:
Despite having ample literature in hepatorenal syndrome–acute kidney injury (HRS-AKI) in decompensated cirrhosis patients, there is a scarcity of data on acute-on-chronic liver failure–acute kidney injury (ACLF-AKI). We compared terlipressin infusion with bolus in ACLF-AKI patients.

Material and methods:
Patients with ACLF (as per the CANONIC study) were screened for AKI as per the 2015 ICA-AKI criteria. If after 48 h of volume expansion with albumin, serum creatinine (sCr) did not improve, patients were randomized into two groups: Terli-infusion (Terli-I) 2 mg/day and Terli-bolus (Terli-B) 1 mg q6h. If sCr did not decrease < 25% of pretreatment value after 48 h, the terlipressin dose was increased to a maximum of 12 mg/day. The primary outcome was taken as regression (full or partial response), stable/no response and progression of AKI to higher stages and secondary outcomes were taken as 28-day and 90-day mortality.

Results:
After screening 136 patients with ACLF-AKI, Terli-I (n = 50) and Terli-B (n = 50) with mean sCr 2.4 and 2.1 mg/dl respectively were enrolled. The regression of AKI (full response 37 vs. 27, partial response 3 vs. 9, p = 0.5), stable (2 vs. 5, p = 0.6), progression of AKI (8 vs. 7, p = 0.2) were present in Terli-I and Terli-B respectively. No significant difference was found in 28-and 90-day mortality. In Terli-B, mean terlipressin dose was 8 vs. 4 mg, p < 0.008 with more side effects, 15 vs. 0, p < 0.01 than Terli-I respectively.

Conclusions:
Terlipressin infusion is more effective than bolus doses in regression of acute kidney injury and better tolerated in acute-on-chronic liver failure–AKI patients.